More than 20 million U.S. women of the Baby Boomer cohort will make th transition to menopause between 2000 and 2010. Despite women's increasing search for information about menopause, little is known about the natural history of the menopausal transition, those years before menopause. Our recent description of an early, middle and late stage of the menopausal transition allows us to continue this 10-year longitudinal study of a group of midlife women with a focus on hormone changes, perceived stress, physiologic stress arousal, symptoms, and depressed mood during three stages of the menopausal transition. An additional focus will be to assess the effects of genetic polymorphisms of the estrogen receptor gene (ESR1 PvuII) and estrogen metabolic genes (CYP17, CYP19, EDH17B2, CYP1A1, CYP1b1 enzymes) on estradiol and estrone levels, age of onset of middle and late transition and menopause, and menstrual bleeding. It is estimated that by the end of this proposed 5-year study the majority of women would have reached late transition or be menopausal. Data collection will involve obtaining a single blood sample for estradiol, a single buccal cell scraping for DNA analysis, four urine samples a year assayed for estrone, FSH, testosterone, cortisol and catecholamines, four 3-day symptom diaries per year, questionnaires, and yearly menstrual calendar. T he results of this study will help inform women and clinicians about normal changes associated with three stages of the menopausal transition and about genetic factors influencing estrogen levels, age of onset of stages of the menopausal transition and menopause and menstrual bleeding.